PROJECT SUMMARY: TUMOR BIOLOGY RESEARCH PROGRAM The Sylvester Comprehensive Cancer Center (Sylvester) Tumor Biology (TB) Research Program, established in 2014, comprises 42 investigators representing 11 departments/disciplines with expertise spanning oncogenic signaling, stress response, developmental pathways, immune signaling, and inflammation. Led by Co-Leaders Wael El-Rifai, MD, PhD, and Ashok Saluja, PhD, the TB program holds a current research funding portfolio of $11.6M in direct peer-reviewed funding, including $5.9M from the National Cancer Institute (NCI). The program facilitates and collaboratively integrates cancer research efforts within the program and center- wide, while catalyzing high-impact discoveries to address the unmet needs of Sylvester?s four-county catchment area. The program?s primary goals are to understand how cancers arise and progress and to define key interactions between cancer cells, tumor stroma, and immune cells. TB members also use that knowledge to identify novel therapeutic approaches that target the fundamental biological and molecular features of cancer cells. To accomplish these goals, TB members have prioritized three scientific aims: 1) Elucidate mechanisms underlying tumor initiation and progression; 2) Determine how inflammation and immunity influence tumorigenesis and the tumor microenvironment; and 3) Investigate the biological and molecular basis of targeted therapeutic approaches. Expertise and technical support from Sylvester?s four shared resources? Biostatistics and Bioinformatics, Onco-Genomics, Flow Cytometry, and Behavioral and Community-Based Research?support TB research efforts. Since 2014, program members have published 337 peer-reviewed, cancer-relevant papers: 33% represent collaborative team science, 21% are intra-programmatic (up from 14% in 2014), 18% are inter-programmatic (up from 13% in 2014), 66% involve collaboration with external institutions, and 28% include scientist from NCI-designated cancer centers. Recent TB research highlights include the discoveries that oxidative stress and antioxidant response promote resistance to androgen deprivation therapy in castration-resistant prostate cancers; aptamer-targeted siRNA approaches can be used to target T cells and enhance anti-tumor immunity; STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors; NACK is an integral component of NOTCH transcription activation complex that can be targeted in cancer cells; a small molecular activator of CK1? (SSTC3) that acts as a novel WNT inhibitor with minimal GI toxicity; and JAK/STAT3 and HSP70 remodel tumor microenvironment and mediate therapeutic resistance in pancreatic cancer. Capitalizing on Sylvester?s infrastructure, the TB Co- Leaders work with program members to promote scientific discoveries and develop new initiatives that leverage emerging scientific ideas and technologies to foster collaborative, innovative, catchment area-relevant basic research.